Preparation of aminocarboxylic acids



Aug. 27, 1957 H. Y. I Ew 7 y PREPARATION 0F AMINOCARBOXYLIC ACIDS Filed June 29, 1953 d 3 B D .1- N om s O m n w 3 o H l O d O v o@ n w. Il. 3 m om o a O M Z o9 .INVENTOR HENRY n EW BYM I ATTORN YS PREPARATION oF AsnNoCARoxYLIC ACIDS Henry Y. Lew, San Francisco, Calif., assignor to California Research Corporation, San Francisco, Calif., a corporation of Delaware Application June 29, 1953, Serial No. 364,545

8 Claims. (Cl. 260-534) The present invention relates to an improved method for the preparation of organo-substituted aminocarboxylic acids containing more than one carboxyalkyl group attached to the nitrogen atom.

More specifically, in the following description the term organo-substituted aminocarboxylic acids containing more than one carboxyalkyl group attached to the nitrogen atom shall refer to N-substituted iminodialkanecarboxylic acids and salts of the formula:

and N-substituted nitrilotrialkane carboxylic acids and salts of the formula:

where R is a hydrocarbon radical containing from 1 to 20 carbon atoms such as alkyl, aryl, cycloalkyl, alkaryl and aralkyl groups n is an integer of 1, 2 or 3 and M, M and MM" are chosen from the group comprising hydrogen, potassium or sodium. Examples of such compounds are N-lauryliminodiacetic acid, disodium N-octadecyl--iminodipropionate, N-phenyl-a-iminodiisobutyric acid, monosodium N-tetradecyl--iminodipropionate and disodium N-methylnitrilotriacetate (disodium N,Ndicar boxymethylglycine methylester), betaine.

The preparation of such organo-substituted aminocarboxylic acids by reaction of primary or secondary amines with halogen-substituted Cz-Cq. aliphatic monocarboxylic acids and salts thereof has been described in the art. This reaction is accompanied by the formation of a free inorganic halogen acid (HC1, HBr, HI or HF), which must be neutralized to prevent a competitive side reaction of the inorganic halogen acid with the amine. In accordance with the prior teachings of the art,neu tralization of the inorganic halogen acids was effected by using sodium hydroxide in the form of aqueous solutions thereof of a suitable strength. However, the employment of aqueous caustic entails considerable disadvantages: When sodium hydroxide is employed in amounts and at concentrations adapted to prevent the inorganic halogen acid-amine side reaction, it causes hydrolysis of the salt of halogen-substituted aliphatic carboxylic acid and formation of a hydroxy-acid. For instance, hydrolysis of sodium chloroacetate results in the formation of glycolic acid. This entails considerable losses of a valuable reactant to undesirable end-products. In some cases, it has been observed, in fact, that the rate of hydrolysis of sodium chloroacetate actually approaches the rate of the reaction of formation of the desired organosubstituted aminocarboxylic acids, and thus necessitates the use of a large excess of sodium chloroacetate to obtain the desired aminocarboxylic acid product. In addition tothe difculties of ascertaining when the desired reaction is nited States Patent hice complete, mixtures of mono, di, and tricarboxymethyl derivatives of the amine are usually obtained.

I have found that these troublesome disadvantages can be substantially eliminated by carrying out the aforementioned reaction of an amine with a halogen-substituted C2-C4 aliphatic acid, or its alkali metal salt, in the presence of sodium bicarbonate.

The attached drawing illustrates the advantages presented by the employment of sodium bicarbonate instead of sodium hydroxide. Curve A of the drawing shows the extent of hydrolysis of sodium chloroacetate as a function of time (in minutes) in the presence of aqueous sodium hydroxide. Curve B strikingly illustrates the almost complete absence of hydrolysis of sodium chloroacetate in the presence of aqueous sodium bicarbonate after two hours or more.

The amount of sodium bicarbonate required to neutralize the inorganic halogen acid formed in the reaction of the amine with the halogen-substituted aliphatic carboxylic acid, or its alkali metal salt, should be suicient to maintain in the reaction mixture a pH of at least 7.0 during the reaction. Thus, in preparing monosodium N-alkyliminodiacetate from one mole of a primary amine and two moles of sodium chloroacetate, at least one mole of sodium bicarbonate is required. Likewise, in preparing monosodium N,Ndicarboxymethyldialkyl amine from one mole of a secondary amine with two moles of sodium chloroacetate, at least one mole of sodium bicarbonate is required. In the reaction of one mole of the primary amine with three moles of sodium chloroacetate, at least two moles of sodium bicarbonate are necessary. An excess of sodium bicarbonate in the reaction mixture may be used without any adverse effect on the pH in the range from 7.0 to 8.5 of the iinal reaction product.

When a diamine is employed in lieu of a monoamine, the number of moles of the halogen-substituted aliphatic acid, or of its alkali metal salt, and of sodium bicarbonate, will be necessarily doubled.

The temperature at which the amine is reacted with the halogen-substituted monocarboxylate and sodium bicarbonate to produce an organo-substituted aminocarboxylic acid in accordance with the present invention, lies in the range from 60 to 100 C., the preferred range being from to 90 C, Even though an excess of sodium bicarbonate may be present in the reaction mixture, the pH will not be higher than 8.5, whereas the pH may be 11.0 and higher in the presence of even a slight excess of sodium hydroxide.

An additional advantage secured through the application of sodium bicarbonate to neutralize the free inorganic acid formed in the production of organo-substituted aminocarboxylic acids, as described and claimed herein, consists in the ability to ascertain the end point of the reaction by the cessation of evolution of the CO2 gas from the reaction vessel.

In the actual practice of the present invention instead of reacting an amine with a halogen-substituted C2-C4 aliphatic acid, an aqueous solution of an alkali metal salt of this acid is prepared iirst and then added to an aqueous solution of the amine and sodium bicarbonate containing, if necessary, a suicient amount of an alcohol (either ethanol or isopropanol) as a solvent for the amine. The mixture is then agitated at 60 to 100 C., but preferably at 80 to 90 C., until no more CO2 gas is evolved.

Amines which may be employed for the reaction are those containing hydrocarbon substituents of 1 to 20 carbon atoms and at least one hydrogen attached to the amino-nitrogen; in other words, their number includes Ci-Czo primary and secondary monoamines and diamines such as alpihatic, aromatic, cycloaliphatic and alkyl aromatic amines. Illustrative examples of monoamines are: octylamine, dodecylamine, stearylamine, phenylamine (aniline), N-methylaniline, naphthylamine, p-methylaniline, dibenzylamine, etc. Primary and secondary alkyl amines containing from 8 to 18 carbon atoms in the alkyl chain are particularly suitable for the purpose. Among the operative diamines may be mentioned phenylenediamine, hexamethylenediamine, ethylenediamne, and the like.

The halogen-substituted C2-C4 aliphatic monocarboxylic acid to be employed for the preparation of the aminocarboxylic acids in accordance with the method of the present invention are preferably monohalogenated saturated C2-C4 aliphatic monocarboxylic acids such as halogenated acetic, propionic and butyric acids. Among the suitable lluoro, chloro-, bromo-, and iodo-substituted C2-C4 aliphatic monocarboxylic acids, the chloro-substitutedacids (acetic, propionic and butyric) are preferred,

chloroacetic acid being generally employed because ofits ready availability.

In the actual practice, it is more convenient to employ alkali metal salts of the afore-described halogen-substituted aliphatic acids, sodium chloroacetate being particularly suitable for the purpose. One may proceed by converting rst the halogen-substituted aliphatic acid, such as chloroacetic, to its salt, as byneutralization with sodium hydroxide (provided a sufliciently low temperature ismaintained to prevent hydrolysis), whereupon sodium bicarbonate can be employed to secure the desired organo-substituted aminocarboxylic acid from a suitable amine and an alkali metal salt such as ClCHzCOONa with the minimum of hydrolysis taking place.

The following examples of the preparation of a representative N-alkyl-substituted iminodiacetic acid, namely, N-lauryldiglycine, further illustrate the improvement attained by employing the method of the present invention over the previous techniques of preparing organo-substituted aminocarboxylic acids which use sodium hydroxide as the neutralizing agent.

Example 1 l mole of straight-chain dodecylamine (C12H25-NH2) is caused to react for 3 hours at a temperature of 85 C. with 2 moles of sodium chloroacetate and l mole of 10% caustic soda solution. The resulting solution is found to contain sodium chloride and about equal amounts of N- laurylglycine and sodium N-lauryliminodiacetate.

Example 2 In this test carried out for 3 hours at 85 C., the same amounts of sodium chloroacetate and dodecylarnine are employed; however, instead of caustic soda solution, sodium bicarbonate is the neutralizing agent. The final solutioncontains sodium chloride and amino-compounds, 90% by weight of which is constituted by sodium N- lauryliminodiacetate and less than by weight of which is N-laurylglycine.

Similar advantages of sodium bicarbonate over' sodium hydroxide in preventing hydrolysis, and securing a substantially unitary organo-substituted aminocarboxylic acid product rather than mixtures of several substituted aminocarboxylic acids, are observed in the tests of preparing other organo-substituted aminocarboxylic acids: e. g., N- stearyliminodiacetic acid and disodium N,NdicarboxymethylglycineV methylester, betaine.

t Among the various organo-substituted aminocarboxylic acids and their N-carboxyalkyl derivatives which can be produced according-to the method of the present invention, N-alkyl aminocarboxylic acids characterized by the presence of straight alkylchains containing from 8 to 18 carbon atoms are particularly attractive, because in addition tobeing amphoteric, they are surface-active and, therefore, lend themselves for the formulation of numerous washing (detergent), foam-improving, levelling and water-softening compositions, as well as for a number of other useful industrial applications.

Itis to be understood that the above'descriptionandV illustrative examples are not limitative of the invention, and Ithat other specic embodiments thereof are to be included within the denitionsof the following claims.

I claim:

l. A method of preparing organo-substituted aminocarboxylic acids having more than one carboxyl group and at least one hydrocarbon substituent with l to 20 carbon atoms attached to the amino-nitrogen atom, which comprises reacting an amine containing at least lone hydrocarbon substituent having from 1 to 20 carbon atoms and at least one hydrogen attached to the amino-nitrogen atom with an alkali metal ysalt of a monohalogen-substituted Cz-C4 aliphatic monocarboxylic acid in the presence of sodium bicarbonate in an amount suici'ent to neutralize the free inorganic halogen acid formed in the reaction.

2. A method of preparing.organo-substituted aminocarboxylic acids having more than one carboxyl group.

and at least one hydrocarbon substituent with 1 to 20 carbon atoms attached to the amino-nitrogen atom, which comprises reacting an lamine containing at least one hydrocarbon substituent having from 1 to 20 carbon atoms and atleast one hydrogen attached to the amino-nitrogen atom with an alkali metal salt of a monohalogen-substituted C2-C4 aliphatic monocarboxylic acid in the presence of sodium bicarbonate in an amount suicient to maintain a pH in the range from 7.0 to 8.5 in the reaction mixture throughout the reaction.

3. A method of preparing organo-substituted aminocarboxylic acids having m-ore than one carboxyl group and one` hydrocarbon substituent having from l to 20 carbon atoms attached to the amino-nitrogen atom, which compri-ses reacting a primary amine having one hydrocarbon substituent of l to- 20 carbon atoms attached to the amino-nitrogen atom with an alkali metal salt of a monohalogen-substituted C2-C4 aliphatic monocarboxylic acid in the presence of sodium bicarbonate in an amount equal to at least 0.5 lmol per each mol of said alkali metal salt and sufficient to neutralize the free inorganic halogen acid Iformed in the reaction.

4. A method of preparing organo-substituted aminocarboxylic acids having two hydrocarbon substituents containing each from l to 20v carbon atoms and attached to the amino-nitrogen atom and, further, having more than one carboxyl group attached to said nitrogen atom, said methodA comprising reacting a secondary amine havingn two hydrocarbon substituents from l to 20 carbon atoms attached to the amino-nitrogen atom, with an alkali metal salt of a monohalogen-substituted C2-C4 aliphatic vlmonocarboxylic acid in the presence of. sodium lbicarbonate in an amount equal t-o at least 0.5 mol per each mol ofy said alkali metal salt and sufficient to neutralize the free inorganic halogen acid formed in the reaction.

5. A rnetho'd of preparing organo-substituted aminocarboxylic acids having two hydrocarbon substituents containing each from l to 2O carbon atoms and attached to the amino-nitrogen atom and, further, having more than one carboxyl group attached to said nitrogen atom, said method comprising reacting a secondary amine having two hydrocarbon substituents Ifrom l to 20 carbon atoms attached to the amino-nitrogen atom, with an alkali metal salt of a monohalogen-substituted (I2-C4 aliphatic monocarboxylic acid in the presence of sodium bicarbonate'in an amount suicient to maintain a pH in the range of.v 7.0 to 8.5 in the reaction product ymixture throughout the reaction.

6. A method of preparing organo-substituted aminocarboxylic acids having more than lone carboxyl group and at least one alkyl substituent with I8 to 18 carbon atomsattached to the amino-nitrogen atom, which comprises reacting a primary alkyl amine containing from 8 to 18 carbon atoms in the alkyl chain-with an alkali metal sal-t ofa halogen-substituted saturated (2z-C4 aliphatic monocarboxylic acid in: the presence ofV sodiurnf bicarbonate in an amount sucient to neutralize the free inorganic halogen acid formed in the reaction to maintain a pH in the range of 7.0 to 8.5 in the reaction product mixture throughout the reaction.

7. A method of preparing organo-substituted aminocarboxylic acids having more than one carboxyl group attached to the amino-nitrogen atom and, further, having two alkyl substituents containing each from 8 to 18 carbon atoms attached to said nitrogen atom, said method comprising reacting a secondary alkyl amine containing `from 8 to 18 carbon atoms in the -alkyl chains attached to the amino-nitrogen atom, with an alkali metal salt of a monohalogen-substituted Cz-C4 aliphatic monocarboxylic acid in the presence of sodium carbonate in an amount suflicient to neutralize the free inorganic halogen acid formed in the reaction to maintain a pH in the range of-7.0 to v8.5 in the reaction product mixture throughout the reaction.

8. A method of preparing N-alkyl-substituted amino-A carboxylic acids having more Ithan one carboxyl group and at least one Cs-Cis straight-chain alkyl substituent attached to the amino-nitrogen atom, which comprises reacting an amine containing at least one Ca-Cis straightchain alkyl chain and at least one hydrogen attached to the amino-nitrogen atom with a sodium salt of a monohalogen-su'bstituted saturated yaliphatic monocarboxylic acid containing from 2 to 4 carbon atoms in the presence of `sodium bicarbonate in an amount suflicient to neutralize the free inorganic halogen acid formed in the reaction to maintain .a pH in the range of 7.0 to 8.5 in the reaction product mixture throughout t-he reaction.

Loder et al. i Apr. 1-3, 1943 Teeters Apr. 13, '1943 

1. A METHOD OF PREPARING ORGANO-SSUBSTITUTED AMINOCARBOXYLIC ACIDS HAVING MORE THAN ONE CARBOXYL GROUP AND AT LEAST ONE HYDROCARBON SUBSTITUENT WITH 1 TO 20 CARBON ATOMS ATTACHED TO THE AMINO-NITROGEN ATOM, WHICH COMPRISES REACTING AN AMINE CONTAINING AT LEAST ONE HYDROCARBON SUBSTITUENT HAVING FROM 1 TO 20 CARBON ATOMS AND AT LEAST ONE HYDROGEN ATTACHED TO THE AMINO-NITROGEN ATOM WITH AN ALKALI METAL SALT OF A MONOHALOGEN-SUBSTITUTED C2-C4 ALIPHATIC MONOCARBOXYLIC ACID IN THE PRESENCE OF SODIUM BICARBONATE IN AN AMOUNT SUFFICIENT TO NEUTRALIZE THE FREE INORGANIC HALOGEN ACID FORMED IN THE REACTION. 